Medical endoprostheses or implants for the widest range of applications are known in a wide variety from the prior art. Implants within the context of the present invention are understood as endovascular prostheses or other endoprostheses, for example, stents, bone attachment elements, for example, screws, plates or pins, surgical suture material, intestinal clamps, vascular clips, prostheses for hard and soft tissue, and anchor elements for electrodes, particularly for pacemakers or defibrillators.
Today, stents are used with particular frequency as implants for treating stenoses (vascular constrictions). They comprise a body in the form of a tubular or hollow cylindrical base lattice, which is open at both longitudinal ends. The tubular base lattice of an endoprosthesis of this type is inserted into the vessel to be treated, and serves to support the vessel. The use of stents to treat vascular diseases has become particularly common. By using stents, constricted areas of the vessels can be dilated, resulting in increased lumen. By using stents or other implants, an optimal vessel cross-section that is primarily necessary for treatment success can be achieved, however, the permanent presence of a foreign body of this type initiates a whole series of microbiological processes, which can lead to a gradual overgrowth of the stent and in the worst case to vascular obstruction.
One approach to solving this problem consists in producing the stent or other implants from a biodegradable material.
Biodegradation is understood to refer to hydrolytic, enzymatic and other metabolic degradation processes in a living organism, which are caused primarily by the bodily fluids coming into contact with the biodegradable material of the implant, and which lead to a gradual dissolution of the structures of the implant that contain the biodegradable material. This process causes the implant to lose its mechanical integrity at a certain time. The term biocorrosion is frequently used as a synonym for the term biodegradation. The term bioabsorption encompasses the subsequent absorption of the degradation products by the living organism.
Materials that are suitable for the body of biodegradable implants can contain polymers or metals, for example. The body can also consist of a plurality of such materials. The feature that is shared by these materials is their ability to biodegrade. Examples of suitable polymeric compounds are polymers from the group of cellulose, collagen, albumin, casein, polysaccharide (PSAC), polylactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D,L-lactide-co-glycolide (PDLLA-PGA), polyhydroxy butyric acid (PHB), polyhydroxy valeric acid (PHV), polyalkyl carbonates, polyortho esters, polyethylene terephthalate (PET), polymalic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids and copolymers thereof, and hyaluronic acid. Each of the polymers can be used in pure form, in derived form, in the form of blends or as copolymers, depending upon the properties desired. The present invention relates to implants containing a metallic biodegradable material based upon magnesium or a magnesium alloy.
Stents that have coatings having different functions are already known in the art. Coatings of this type are used, for example, for releasing medications, positioning an x-ray marker, or protecting the structures that lie beneath said coatings.
In implementing biodegradable implants, the degradability thereof is controlled based upon the desired treatment or the use of the respective implant (coronary, intracranial, renal, etc.). For many therapeutic applications, for example, an important target range involves the implant losing its integrity over a period of four weeks to six months. In this context, integrity, i.e., mechanical integrity, is understood as the property that the implant has virtually no mechanical losses in relation to non-degraded implants. This means that the implant is still mechanically stable enough that, for example, the pressure to collapse drops only slightly, i.e., at most to 80% of the nominal value. Therefore, the implant is still able to perform, with maintenance of the integrity of its primary function, supporting the vessel. Alternatively, the integrity can be defined by the fact that the implant is mechanically stable enough that in its load state in the vessel, it is subject to almost no geometric changes, for example, it is not markedly compressed, i.e., under stress it retains at least 80% of its dilation diameter, or in the case of a stent, has almost no fractured supporting struts.
Biodegradable magnesium implants, particularly magnesium stents, have proven particularly promising for the stated target range of degradation, however, these implants still lose their mechanical integrity or supportive effect too early, and still have a severely fluctuating loss of integrity in vitro and in vivo. This means that with magnesium stents, the collapse pressure decreases too rapidly over time, or the decrease in the collapse pressure has too much variability and is therefore too indeterminable.
Various mechanisms for controlling the degradation of magnesium implants are already described in the prior art. These are based, for example, on inorganic and organic protective layers or combinations thereof, which offer resistance to the human corrosion milieu and the corrosive processes occurring therein. Solutions known in the prior art are characterized in that boundary layer effects are achieved, which involve a spatial and, if possible, defect-free separation of the corrosive medium from the metallic material, particularly the metallic magnesium. For instance, protection against degradation is ensured by various combined protective layers and by defined geometric distances (diffusion barriers) between the corrosive medium and the magnesium base material. Additional solutions in the field of controlled degradation produce predefined fracture effects by the application of physical (e.g., localized cross-sectional changes) and/or chemical changes to the stent surface (e.g., localized chemically differently composed multilayers). However, the above-mentioned solutions have as yet failed, for the most part, to place the dissolution produced by the degradation process and the resulting strut breaks within the required window of time. The result is degradation of the implant that begins either too early or too late, or is too widely variable.
A further problem associated with coatings results from the fact that stents or other implants ordinarily take on two states, specifically a compressed state in which they have a small diameter, and a dilated state, in which they have a larger diameter. In the compressed state, the implant can be inserted by means of a catheter into the vessel to be supported, and can be positioned at the site to be treated. At the treatment location, the implant is then dilated by means of a balloon catheter, for example. This change in diameter subjects the body of the implant to mechanical stress. Additional mechanical stresses on the implant can occur during production or with the movement of the implant in or with the vessel into which the implant is inserted. Therefore, with the stated coatings according to the prior art, the disadvantage results that the coating tears (e.g., formation of microcracks) or is even partially removed during deformation of the implant. This can result in an unspecified localized degradation. In addition, the onset and the speed of degradation are dependent upon the size and the distribution of the microcracks resulting from the deformation, which as defects cannot be easily controlled. This results in a large deviation in degradation times.
Additional examples of known organic or inorganic protective layers for increasing resistance to degradation include galvanic coatings with zinc, coatings based on ionic liquids, conversion coatings involving chemical conversion of the main alloy constituents, vaporization or sputtering with aluminum, thermal spraying, etc.
Higher alloyed parent materials are also used for improving resistance to degradation. For instance, for years, magnesium alloys containing rare earths (e.g., alloy WE 43) have been used as stent material. For many applications, these materials have an advantageous combination of adequate mechanical properties and good corrosion resistance. Therefore, they have a greater potential for use in absorbable implants as compared with non-alloyed magnesium.
From document WO 2011/051424 A1, an implantable medical device is known, which is made at least partially of a material that contains highly pure magnesium or a magnesium alloy with highly pure magnesium and one or more additional highly pure alloy constituents. Highly pure alloy constituents can be the elements indium, scandium, yttrium, gallium and the rare earths, wherein highly pure gallium is present in the alloy in amounts of 0.1 wt % to 5 wt %. The production of such highly pure materials is very costly, and therefore, the costs of the medical apparatus are also high.
Document WO 2007/0207186 A1 lists a series of additives which improve the properties of an implant. In this case, however, the modified properties of the implant are not described in detail in terms of the respective additive.